Intraoperative direct cortical stimulation motor evoked potentials: Stimulus parameter recommendations based on rheobase and chronaxie.

OBJECTIVE: To determine optimal interstimulus interval (ISI) and pulse duration (D) for direct cortical stimulation (DCS) motor evoked potentials (MEPs) based on rheobase and chronaxie derived with two techniques. METHODS: In 20 patients under propofol/remifentanil anesthesia, 5-pulse DCS thenar MEP rheobase and chronaxie with 2, 3, 4 and 5ms ISI were measured by linear regression of five charge thresholds at 0.05, 0.1, 0.2, 0.5 and 1msD, and estimated from two charge thresholds at 0.1 and 1msD using simple arithmetic. Optimal parameters were defined by minimum threshold energy: the ISI with lowest rheobase2×chronaxie, and D at its chronaxie. Near-optimal was defined as threshold energy <25% above minimum. RESULTS: The optimal ISI was 3 or 4 (n=7 each), 2 (n=4), or 5ms (n=2), but only 4ms was always either optimal or near-optimal. The optimal D was ∼0.2 (n=12), ∼0.1 (n=7) or ∼0.3ms (n=1). Two-point estimates closely approximated five-point measurements. CONCLUSIONS: Optimal ISI/D varies, with 4ms/0.2ms being most consistently optimal or near-optimal. Two-point estimation is sufficiently accurate. SIGNIFICANCE: The results endorse 4ms ISI and 0.2msD for general use. Two-point estimation could enable quick individual optimization.

Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.

Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD) curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms. Axons are thus more excitable at short time scales, but at longer time scales dendrites are more easily excited. We complement these studies with experiments on fully connected cultures. An explanation for the chronaxie of dendrites is found in the numerical simulations of passive, realistically structured dendritic trees under external stimulation. The much shorter chronaxie of axons is not captured in the passive model and may be related to active processes. The lower rheobase of dendrites at longer durations can improve brain stimulation protocols, since in the brain dendrites are less specifically oriented than axonal bundles, and the requirement for precise directional stimulation may be circumvented by using longer duration fields.

Limb immobilization alters functional electrophysiological parameters of sciatic nerve.

Immobilization, used in clinical practice to treat traumatologic problems, causes changes in muscle, but it is not known whether changes also occur in nerves. We investigated the effects of immobilization on excitability and compound action potential (CAP) and the ultrastructure of the rat sciatic nerve. Fourteen days after immobilization of the right leg of adult male Wistar rats (n=34), animals were killed and the right sciatic nerve was dissected and mounted in a moist chamber. Nerves were stimulated at a baseline frequency of 0.2 Hz and tested for 2 min at 20, 50, and 100 Hz. Immobilization altered nerve excitability. Rheobase and chronaxy changed from 3.13 ± 0.05 V and 52.31 ± 1.95 µs (control group, n=13) to 2.84 ± 0.06 V and 59.71 ± 2.79 µs (immobilized group, n=15), respectively. Immobilization altered the amplitude of CAP waves and decreased the conduction velocity of the first CAP wave (from 93.63 ± 7.49 to 79.14 ± 5.59 m/s) but not of the second wave. Transmission electron microscopy showed fragmentation of the myelin sheath of the sciatic nerve of immobilized limbs and degeneration of the axon. In conclusion, we demonstrated that long-lasting leg immobilization can induce alterations in nerve function.

Limb immobilization alters functional electrophysiological parameters of sciatic nerve

Immobilization, used in clinical practice to treat traumatologic problems, causes changes in muscle, but it is not known whether changes also occur in nerves. We investigated the effects of immobilization on excitability and compound action potential (CAP) and the ultrastructure of the rat sciatic nerve. Fourteen days after immobilization of the right leg of adult male Wistar rats (n=34), animals were killed and the right sciatic nerve was dissected and mounted in a moist chamber. Nerves were stimulated at a baseline frequency of 0.2 Hz and tested for 2 min at 20, 50, and 100 Hz. Immobilization altered nerve excitability. Rheobase and chronaxy changed from 3.13±0.05 V and 52.31±1.95 µs (control group, n=13) to 2.84±0.06 V and 59.71±2.79 µs (immobilized group, n=15), respectively. Immobilization altered the amplitude of CAP waves and decreased the conduction velocity of the first CAP wave (from 93.63±7.49 to 79.14±5.59 m/s) but not of the second wave. Transmission electron microscopy showed fragmentation of the myelin sheath of the sciatic nerve of immobilized limbs and degeneration of the axon. In conclusion, we demonstrated that long-lasting leg immobilization can induce alterations in nerve function.

Strength-duration relationship for intra- versus extracellular stimulation with microelectrodes.

Chronaxie, a historically introduced excitability time parameter for electrical stimulation, has been assumed to be closely related to the time constant of the cell membrane. Therefore, it is perplexing that significantly larger chronaxies have been found for intracellular than for extracellular stimulation. Using compartmental model analysis, this controversy is explained on the basis that extracellular stimulation also generates hyperpolarized regions of the cell membrane hindering a steady excitation as seen in the intracellular case. The largest inside/outside chronaxie ratio for microelectrode stimulation is found in close vicinity of the cell. In the case of monophasic cathodic stimulation, the length of the primarily excited zone which is situated between the hyperpolarized regions increases with electrode-cell distance. For distant electrodes this results in an excitation process comparable to the temporal behavior of intracellular stimulation. Chronaxie also varies along the neural axis, being small for electrode positions at the nodes of Ranvier and axon initial segment and larger at the soma and dendrites. As spike initiation site can change for short and long pulses, in some cases strength-duration curves have a bimodal shape, and thus, they deviate from a classical monotonic curve as described by the formulas of Lapicque or Weiss.

A comparison of the excitability of motor axons innervating the APB and ADM muscles.

OBJECTIVE: Threshold tracking allows the non-invasive assessment of axonal excitability. This study aimed to determine whether axonal excitability of the motor axons of the median nerve (to APB) and ulnar nerve (to ADM) to the small muscles of the hands is sufficiently similar to be interchangeable; confirm the feasibility and reproducibility of ulnar studies and obtain control data for a young population for this site of stimulation. METHODS: Twenty normal subjects between the ages of 23-43 were studied using the TRONDF protocol of QTRACS, (©Prof Hugh Bostock, London). The median and ulnar nerves were stimulated at the wrist and the compound muscle action potentials were recorded from abductor pollicis brevis and abductor digiti minimi, respectively. Repeat studies were performed in four subjects to confirm reproducibility of the recordings. RESULTS: Stimulus intensity was greater and strength duration time constant was longer for the median nerve. Threshold electrotonus showed there was a greater change in threshold in the hyperpolarising direction for the median nerve compared with the ulnar nerve. There was however little difference in the recovery cycle and current threshold relationship. CONCLUSIONS: Although recovery cycles and the current thresholds are similar for APB and ADM, there are definite differences in stimulus threshold, SDTC and threshold electrotonus which question the interchangeability of studies for these two sites. SIGNIFICANCE: This study demonstrates reproducibility of motor axonal excitability studies of the ulnar nerve at the wrist, provides young control data for this site of stimulation and suggests that although certain excitability indices are similar for the median nerve to APB and ulnar nerve to ADM there are definite differences making the interchangeability of the data questionable.

A model for transcutaneous current stimulation: simulations and experiments.

Complex nerve models have been developed for describing the generation of action potentials in humans. Such nerve models have primarily been used to model implantable electrical stimulation systems, where the stimulation electrodes are close to the nerve (near-field). To address if these nerve models can also be used to model transcutaneous electrical stimulation (TES) (far-field), we have developed a TES model that comprises a volume conductor and different previously published non-linear nerve models. The volume conductor models the resistive and capacitive properties of electrodes, electrode-skin interface, skin, fat, muscle, and bone. The non-linear nerve models were used to conclude from the potential field within the volume conductor on nerve activation. A comparison of simulated and experimentally measured chronaxie values (a measure for the excitability of nerves) and muscle twitch forces on human volunteers allowed us to conclude that some of the published nerve models can be used in TES models. The presented TES model provides a first step to more extensive model implementations for TES in which e.g., multi-array electrode configurations can be tested.

The hyperbolic strength-duration relationship of defibrillation threshold.

Defibrillation with square-wave pulses has proved to possess hyperbolic strength-duration relationship. Does such a hyperbolic relation also exist for exponentially decaying pulses as they are commonly used today? This paper hypothesizes that exponentially decaying pulses obey hyperbolic strength-duration relationship, calculates the consequences, and advises of how such thresholds should be investigated. If the strength-duration relationship exists for current, the corresponding charge threshold must be a Weiss' straight threshold line. In analogy, for exponentially decaying pulses, the integral of the amplitude over pulse duration (PD) must be calculated as a function of PD. If this function is linearly correlated, the mean voltage possesses a hyperbolic strength-duration relationship, whereas the peak voltage does not. Peak amplitude curves possess minima shifting to the right with increasing time constant RC limiting the allowed range of useful PDs. To prove that exponentially decaying pulses have a hyperbolic relationship, testing must be done in six steps that are demonstrated with results published in literature. Mean voltages have, indeed, hyperbolic strength-duration relationship. Chronaxie is not calculated correctly as long as peak voltage thresholds are correlated and PDs are greater than allowed.

Multichannel surface recordings on the visual cortex: implications for a neuroprosthesis.

Using a multi-channel platinum surface electrode array, recordings from cat primary visual cortex were obtained in response to visual stimuli, and electrical stimuli delivered using the elements of the array itself. Neural responses to electrical stimuli were consistent, regardless of stimulus polarity or leading phase (biphasic), although thresholds were lower for monophasic than biphasic pulses. Both visual and electrical stimuli reliably evoked responses with characteristic components, which interacted with each other in a nonlinear summation showing first facilitation then suppression during the window of interaction. The chronaxie for eliciting threshold cortical responses was about 100 mus, and the charge density with a pulse width of 50-100 mus was around 55 muC cm(-2). These data form the basis of understanding the types of cortical responses to stimuli delivered by devices suitable for chronic implantation.

Electrical stimulation based on chronaxie reduces atrogin-1 and myoD gene expressions in denervated rat muscle.

Denervation induces muscle fiber atrophy and changes in the gene expression rates of skeletal muscle. Electrical stimulation (ES) is a procedure generally used to treat denervated muscles in humans. This study evaluated the effect of ES based on chronaxie and rheobase on the expression of the myoD and atrogin-1 genes in denervated tibialis anterior (TA) muscle of Wistar rats. Five groups were examined: (1) denervated (D); (2) D+ES; (3) sham denervation; (4) normal (N); and (5) N+ES. Twenty muscle contractions were stimulated every 48 h using surface electrodes. After 28 days, ES significantly decreased the expression of myoD and atrogin-1 in D+ES compared to the D group. However, ES did not prevent muscle-fiber atrophy after denervation. Thus, ES based on chronaxie values and applied to denervated muscles using surface electrodes, as normally used in human rehabilitation, was able to reduce the myoD and atrogin-1 gene expressions, which are related to muscular growth and atrophy, respectively. The results of this study provide new information for the treatment of denervated skeletal muscle using surface ES.

Comments on "accuracy limitations of chronaxie values".

Some additions/corrections are offered to Geddes, 2004. Stimulation is initiated by the second spatial derivative of the voltage along the nerve (activating function) rather than current density. Chronaxie values change with distance from the electrode. Anodic stimulation can excite via anodic break excitation, or via virtual cathodes around the anode.

Temporal excitation properties of paresthesias evoked by thalamic microstimulation.

OBJECTIVE: The neuronal elements mediating the effects of deep brain stimulation (DBS) are unknown. The objective was to determine the strength-duration properties of the neuronal elements that mediate paresthesias evoked by thalamic microstimulation. METHODS: The strength-duration properties of the neuronal elements causing paresthesias were measured using intraoperative microstimulation of the human thalamus. The sample included both concordant (reported in the same region as the mapped sensory receptive fields) and discordant paresthesias (reported in a region different than the mapped sensory receptive fields). RESULTS: There were no significant differences between the chronaxies of concordant and discordant paresthesias. There was no significant correlation between chronaxie and rheobase for concordant paresthesias, but a strong negative correlation existed for discordant paresthesias. CONCLUSIONS: Chronaxies did not distinguish the neuronal elements mediating concordant and discordant paresthesias, but correlations between chronaxie and rheobase suggest that concordant paresthesias were produced by activation of local cells while discordant paresthesias were caused by activation of axons of passage. SIGNIFICANCE: The similarity between the strength-duration properties of paresthesias evoked by thalamic stimulation, tremor reduction evoked by thalamic DBS, and EMG responses to thalamic DBS does not mean that these effects are caused by the same neural elements.

Accuracy limitations of chronaxie values.

The strength-duration curve is a plot of the threshold current (I) versus pulse duration (d) required to stimulate excitable tissue. On this curve are two points: 1) rheobase (b) and 2) chronaxie (c). Rheobase is the threshold current for an infinitely long-duration stimulus. Chronaxie, the excitability constant, is the duration of a pulse of current of twice rheobasic strength. The mathematical expression for the strength-duration curve is I = b(1 + c/d). Although there are many published values for chronaxie for various excitable tissues, the range of variability for a given tissue type is quite large. This paper identifies five factors that can affect the accuracy of chronaxie measurement and shows that the most reliable values can be obtained with a rectangular pulse delivered from a constant-current source.

Sensitivity of temporal excitation properties to the neuronal element activated by extracellular stimulation.

Measurements of the chronaxies and refractory periods with extracellular stimuli have been used to conclude that large diameter axons are responsible for the effects of deep brain stimulation (DBS). We hypothesized that because action potential initiation by extracellular stimulation occurs in the axons of central nervous system (CNS) neurons, the chronaxies and refractory periods determined using extracellular stimulation would be similar for cells and axons. Computer simulation was used to determine the sensitivity of chronaxie and refractory period to the neural element stimulated. The results demonstrate that chronaxies and refractory periods were dependent on the polarity of the extracellular stimulus and the electrode-to-neuron distance, and indicate that there is little systematic difference in either chronaxies or refractory periods between local cells or axons of passage with extracellular stimulation. This finding points out the difficulty in drawing conclusions regarding which neuronal elements are activated based on extracellular measurements of temporal excitation properties.

Beneficio potencial de la electroestimulacion neuromuscular del cuadriceps femoralpara el fortalecimiento / The potential benefit of neuro-muscular eletro-stimulation of the femoral quadriceps for strengthening

La eficiencia de la estimulación eléctrica en el músculo sano es discutida; en este estudio se cuantifican las fuerzas generadas con diversas corrientes y se determinan algunas condiciones óptimas del impulso excitomotor. En 15 sujetos se miden la cronaxia muscular y, mediante un dispositivo ergométrico, la fuerza de la contracción máxima voluntaria del cuádriceps femoral y el porcentaje de esta fuerza electroinducido con corrientes bifásicas de baja frecuencia y distinta duración de pulso y frecuencia tetanizante, con corriente farádica y con corriente de media frecuencia en aplicación interferential, en el nivel dé intensidad de máxima tolerancia. Se confirma la relación proporcional de la duración del estímulo con la intensidad de corriente soportada y la fuerza evocada; los impulsos de 300 useg precisan menor intensidad de corriente bifásica y producen contracciones más intensas en el músculo examinado que estímulos de duración inferior a 200 useg., no habiendo diferencia de la fuerza obtenida en 50 y 70 Hz; tampoco hay proporcionalidad entre la intensidad de corriente emitida y el porcentaje de fuerza máxima desarrollada. Las intensidades toleradas de corriente farádica e interferential son similares a las de corriente bifásica con pulso de 300 useg. pero en ésta última la cantidad de electricidad, ligada a la sensación nociceptiva, resulta inferior y los picos de fuerza superiores y suficientes potencialmente para un efecto de fortalecimiento a diferencia de las otras aplicaciones (AU)

Immediate motor effects of stimulation through electrodes implanted in the human globus pallidus.

The immediate motor effects of stimulation through electrodes chronically implanted in the globus pallidus internus (GPI) were studied in 9 subjects with Parkinson's disease. Single stimuli (at >>0.4 Hz) produced short latency facilitation of voluntarily activated contralateral muscles in all subjects. The latency and distribution of the facilitation, its probably monosynaptic nature, and the short chronaxie and refractory period of the activated neural elements suggest that the facilitation results from the direct excitation of the fast conducting corticospinal pathway. The facilitation of motoneurons followed high frequency (e.g. 200 Hz) stimulation without decrement and occurred at stimulus intensities well below those required to produce a visible muscle contraction. We conclude that, while there may be other effects, GPI stimulation through electrodes may activate the corticospinal tract, even when the stimuli are below the threshold for a visible muscle contraction, and that continuous stimulation may do so continuously. This may be an unwanted side effect, but possible therapeutic actions are considered. The reproducible short latency facilitation enabled us to estimate current spread from the quadripolar electrodes used for deep brain stimulation. When the current is sufficient to excite large myelinated fibers near one of the quadripolar electrodes, an additional 1-mA current will activate similar fibers at an additional distance of 1.8 mm with bipolar stimulation and at a distance of 5.7 mm with monopolar stimulation.

The zeta pulse: a new stimulus waveform for use in electrical stimulation of the nervous system.

A new waveform which can be used instead of pulses for general electrical stimulation of the nervous system is described. This new waveform has been called the 'Zeta' pulse. The potential advantages of the use of this waveform are discussed together with a brief review and discussion of the mechanisms of extracellular stimulation in nervous tissue. A circuit diagram for the generation of the Zeta waveform is given.

Electrically evoked saccades from the dorsomedial frontal cortex and frontal eye fields: a parametric evaluation reveals differences between areas.

Using electrical stimulation to evoke saccades from the dorsomedial frontal cortex (DMFC) and frontal eye fields (FEF) of rhesus monkeys, parametric tests were conducted to compare the excitability properties of these regions. Pulse frequency and pulse current, pulse frequency and train duration, and pulse current and pulse duration were varied to determine threshold functions for a 50% probability of evoking a saccade. Also a wide range of frequencies were tested to evoke saccades, while holding all other parameters constant. For frequencies beyond 150 Hz, the probability of evoking saccades decreased for the DMFC, whereas for the FEF this probability remained at 100%. To evoke saccades readily from the DMFC, train durations of greater than 200 ms were needed; for the FEF, durations of less than 100 ms were sufficient. Even though the chronaxies of neurons residing in the DMFC and FEF were similar (ranging from 0.1 to 0.24 ms) significantly higher currents were required to evoke saccades from the DMFC than FEF. Thus the stimulation parameters that are optimal for evoking saccades from the DMFC differ from those that are optimal for evoking saccades from the FEF. Although the excitability of neurons in the DMFC and FEF are similar (due to similar chronaxies), we suggest that the density of saccade-relevant neurons is higher in the FEF than in the DMFC.

Blockade of sensory neuron action potentials by a static magnetic field in the 10 mT range.

To characterize the inhibitory effect of a static magnetic field, action potentials (AP) were elicited by intracellular application of 1 ms depolarizing current pulses of constant amplitude to the somata of adult mouse dorsal root ganglion neurons in monolayer dissociated cell culture. During the control period, < 5% of stimuli failed to elicit AP. During exposure to an approximately 11 mT static magnetic field at the cell position produced by an array of four permanent center-charged neodymium magnets of alternating polarity (MAG-4A), 66% of stimuli failed to elicit AP. The number of failures was maximal after about 200-250 s in the field and returned gradually to baseline over 400-600 s. A direct or indirect effect on the conformation of AP generating sodium channels could account for these results because 1) failure was preceded often by reduction of maximal rate of rise, an indirect measure of sodium current; 2) recovery was significantly prolonged in more than one-half of neurons that were not stimulated during exposure to the MAG-4A field; and 3) resting membrane potential, input resistance, and chronaxie were unaffected by the field. The effect was diminished or prevented by moving the MAG-4A array along the X or Z axis away from the neuron under study and by increasing the distance between magnets in the XY plane. Reduction of AP firing during exposure to the approximately 0.1 mT field produced by a MAG-4A array of micromagnets was about the same as that produced by a MAG-4A array of the large magnets above. The approximately 28 mT field produced at cell position by two magnets of alternating polarity and the approximately 88 mT field produced by a single magnet had no significant effect on AP firing. These findings suggest that field strength alone cannot account for AP blockade.